The pluripotency factor Lin28 blocks the expression of let-7 microRNAs in undifferentiated cells during development and functions as an oncogene in a subset of cancers. Lin28 binds to let-7 precursor RNAs and recruits 3′ terminal uridylyl transferases (TUTases) to selectively inhibit let-7 biogenesis. Uridylated pre-let-7 is refractory to processing by Dicer and is rapidly degraded by an unknown ribonuclease.